Hereditary equine regional dermal asthenia (HERDA) is an inherited skin disease predominantly found in the American Quarter Horse. The classic phenotype of velvety hyperextensible skin, accompanied with seromas and hematomas particularly along the dorsal aspect, does not normally present until sometime after 6 months of age, often as old as two years when the horse is first being broke to saddle. The inability to treat the disease most commonly results in euthanasia of the affected horse. While there have been relatively few HERDA (historically, also referred to as hyperelastosis cutis) cases reported throughout the past thirty years, an increase in the incidence of HERDA cases being seen by veterinary dermatologists occurred in the late 1990's.
Pedigree analysis suggests an autosomal recessive mode of inheritance, with a common ancestor that can be traced back via both the paternal and maternal lines in all HERDA cases with complete pedigrees. Heritability analysis corroborated those conclusions drawn from pedigree analysis and calculated increased inbreeding coefficient values for HERDA horses relative to a random sampling of American Quarter Horses [Tryon et al., Am J Vet Res, 66(3): p. 437-42 (2005)]. Analysis of sire records of stallions known to produce offspring with HERDA estimated a carrier frequency of 2-6% in the sub-population of mares being bred to those horses.
The HERDA phenotype shares similarities with clinical diagnoses seen in humans and animals, yet specific features of the disease pathology suggest it may have a unique genetic basis. Ehlers-Danlos Syndrome (EDS) is a heterogenic disorder that can take a variety of forms in humans, but a universal characteristic of the condition is fragile hyperextensible skin that can be more easily subject to bruising and tearing [Mao, J. R. and J. Bristow, J Clin Invest, 107(9): p. 1063-9 (2001)]. Many forms of EDS affect skin regardless of the location on the body and do not require a trigger event to display the phenotype. The common thread to the variety of genes in which mutations have been associated with EDS is the fibril collagens. The majority of cases displaying the gross EDS phenotype are caused by defects in the collagen genes themselves (COL1A1, COL3A1, COL5A, COL5A2) or in the enzymes which process (ADAMTS2, PLOD) or interact (TNXB) with collagens.
In contrast, HERDA foals rarely show indications of the disease at birth and areas which develop lesions are non-uniformly distributed over the body. Many cases of HERDA are not identified until the horses begin to train with a saddle, and lesions are most commonly found along the dorsal aspect, coincident with where the saddle would rest. Histological examination of HERDA tissue could not definitively diagnose the disease, although subtle signs of thinned and shortened collagen fibers in the deep dermis suggest a general disorganization in affected individuals [White et al., Vet Dermatol, 15(4): p. 207-17 (2004)]. Collagen 1 and collagen 3 content were indistinguishable between HERDA samples and unaffected controls [White et al., Vet Dermatol, 15(4): p. 207-17 (2004)].
Thus, there is a need in the art for compositions and methods for accurately identifying equines that are HERDA carriers as well as for diagnosing whether an equine is afflicted with HERDA. The present invention meets these and other needs.